Gait abnormalities, ADHD, and environmental exposure to nitrous oxide

Area of Science:

• Neuroscience
• Developmental Psychology
• Environmental Health

Background:

• Attention-deficit hyperactivity disorder (ADHD) is associated with altered gait profiles, particularly in children with the combined type (ADHD-CT).
• A maturational delay hypothesis suggests gait variability decreases with age in children with ADHD.
• Cognitive impairments in ADHD are hypothesized to stem from chronic exposure to environmental pollutants like nitrous oxide (N2O).

Discussion:

• Nitrous oxide (N2O) exposure may induce antinociceptive effects by stimulating dynorphin peptide release, acting on kappa opioid receptors (KOR).
• Evidence links prodynorphin mutations in mice to abnormal gait and motor coordination due to elevated dynorphin A (DYN A) levels.
• Altered gait profiles in ADHD could be linked to enhanced opioidergic activity from N2O exposure.

Key Insights:

• Children with ADHD-CT show significant differences in gait profiles compared to typically developing (TD) controls, especially at faster speeds.
• Chronic exposure to the air pollutant nitrous oxide (N2O) is proposed as a potential cause for cognitive and gait impairments in ADHD.
• Dynorphin peptides and kappa opioid receptors (KOR) are implicated in the opioid-mediated gait abnormalities observed in ADHD.

Outlook:

• Maturational changes in KOR constitutive activity in the brain may explain the normalization of gait profiles in older individuals with ADHD.
• Further research is needed to elucidate the precise mechanisms linking N2O exposure, opioidergic systems, and gait development in ADHD.
• Investigating environmental factors like N2O offers a novel perspective for understanding and potentially managing ADHD-related gait disturbances.